Fluids from the male reproductive tract contain immuno-regulatory substances which protect sperm from attack by the immune system. These immuno-regulatory substances have been shown to be potent inhibitors of complement action, lymphocyte activation and antibody production. Sertoli cells from the testis secrete the components of the fluid of the seminiferous tubules and contribute to the composition of seminal fluid. Sertoli cells in culture secrete a number of glycoproteins which are normally constituents of this fluid. The secretion products of the Sertoli cells contain similar immuno-regulatory activities to those described for seminal fluids. It is the long-term goal of this proposal to isolate, purify and characterize the factors in the Sertoli cell secretions which are responsible for this immuno-regulatory activity. The immediate goals of the research include the following specific aims: 1. To determine the complete spectrum of immuno-regulatory activities present in the Sertoli cell secreted proteins. Assays will be run to determine if the secreted proteins inhibit antibody production, macrophage function, suppressor cell function, cytotoxic activity as well as lectin induced mitogenesis and complement mediated lysis. 2. The factors responsible for the immunological regulatory activities will be isolated and purified by standard biochemical methods including HPLC. 3. The mechanism(s) by which these purified factors exert their activities will be examined in a series of assays designed to examine in more detail the activities described in specific aim 1. Results from these studies could be important in our understanding of the basis of immunological infertility and genital tract-related diseases.